Few sampling systems supplied with laboratory fermenters are easily modified for unattended aseptic sampling. Most commercial sampling systems are manually operated. They are either hooded samplers or bottom-harvesting valves. The former operate on a vaccum principle and are widely accepted as being safe and simple for culture sampling. They can be sterilized either separately or with the culture vessel. During operation, aseptic conditions are maintained by a break in the liquid stream, along with the hood on the exit line. The latter -- bottom harvesting valves -- are usually found on larger (2-25 L) fermentation vessels. They use in situ steam sterilizable diaphragms or piston valves. These valves are easily sterilized between sampling times and are very reliable.
An automated, computer controlled HPLC system is described by R.C. Dinwoodie et al in Biotechnology and Bioengineering, Vol. XXVII, pp. 1060-1062 (1985). The system is equipped with a continuous flow-through sample vial for the on-line analysis of fermentation broths. A peristaltic pump withdraws a stream from the fermenter, passes it through a filtration unit and then through the vial. The stream and the filtered cells are returned to the fermenter.
Another sampling device is described in Biotechnology and Engineering, Vol. XXVIII, pp. 119-121 (1986) by M. Ghoul et al. This device has a recirculation loop with a proportioning peristaltic pump and four three-way sterilizable valves. A continuous band of ultrafiltration membranes is provided to filter the sample drawn from a fermenter. The filtration surface is renewed after each sample. A cuvette is provided to receive the samples after filtration. The entire sampling system is controlled by a microcomputer. Steam sterilization of the circuit is available to prevent its contamination with microorganisms.
While these prior art devices are useful, there is still a need for a simple and reliable sampling system that is useful, for instance, for batch yeast fermentation lasting 12 to 24 hours. In particular, it is an object of the present invention to develop a sampling system wherein the often large dead volume would be reduced to a minimum.